p21 regulates the HIV-1 restriction factor SAMHD1

p21 regulates the HIV-1 restriction factor SAMHD1

Online publication: 07/03/2014 Printed publication: 8 April 2014 Journal: Proceedings of the National Academy of Sciences

Abstract:

Allouch et al. have shown that CDKN1A (p21) restricts HIV-1 replication in monocyte-derived macrophages (MDM) by controlling the expression of the ribonucleotide reductase subunit R2 (RNR2) of the ribonucleotide reductase enzyme that, in turn, controls the intracellular deoxynucleotide (dNTP) pool required for HIV-1 reverse transcription. dNTP levels are also tightly controlled by the dNTP triphosphohydrolase SAM domain and HD domain-containing protein 1 (SAMHD1), which is constitutively expressed in myeloid and lymphoid cells and is counteracted by the lentiviral virus protein x (Vpx) (reviewed in ref. 2). SAMHD1 is deactivated in proliferating cells by a mechanism that requires phosphorylation of SAMHD1 . Allouch et al. conclude that p21-driven HIV-1 restriction in macrophages is independent of SAMHD1 because (i) p21 did not affect SAMHD1 expression and (ii) Vpx did not affect p21 expression.

Authors: Pauls, Eduardo; Ruiz, Alba; Riveira-Munoz, Eva; Permanyer, Marc; Badia, Roger; Clotet, Bonaventura; Keppler, Oliver T.; Ballana, Ester; Este, Jose A

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